Weight-Based Compared With Fixed-Dose Enoxaparin Prophylaxis After Cesarean Delivery: A Randomized Controlled Trial.

Objective: To evaluate fixed compared with weight-based enoxaparin dosing to achieve prophylactic anti-Xa levels after cesarean delivery.

Methods: Individuals meeting institutional criteria for enoxaparin thromboprophylaxis after cesarean delivery were randomly allocated to fixed (40 mg daily for body mass index [BMI, calculated as weight in kilograms divided by height in meters squared] lower than 40; 40 mg every 12 hours for BMI 40 or higher) or weight-based (0.5 mg/kg every 12 hours) enoxaparin dosing. Enoxaparin was initiated during inpatient hospitalization and continued at discharge for 14 days. Those with contraindication to anticoagulation, plan for therapeutic anticoagulation, or known renal impairment were excluded. The trial was unmasked. The primary outcome was prophylactic (0.2-0.6 international units/mL) peak anti-Xa level 4-6 hours after at least the third enoxaparin dose (at steady state). Secondary outcomes included subprophylactic and supraprophylactic peaks, outpatient peak, and venous thromboembolism (VTE) and wound complications in the first 6 weeks postpartum. Sample size of 121 per group was planned. At interim analysis with 50% enrollment, the trial was stopped early for efficacy. Primary analyses followed intention-to-treat principle with worst-case imputation for missing outcomes. Secondary analyses were complete case.

Results: From June 2020 to November 2021, 74 individuals were randomized to weight-based enoxaparin and 72 to fixed-dose enoxaparin. Those who received weight-based dosing were more likely to achieve prophylactic anti-Xa levels than those who received fixed dosing in primary analysis (49/74 [66%] vs 32/72 [44%], relative risk [RR] 1.49, 95% CI 1.10-2.02) and secondary analysis (49/60 [82%] vs 32/57 [56%], RR 1.45, 95% CI 1.12-1.88). Subprophylactic levels occurred more frequently with fixed dosing; supraprophylactic levels did not differ significantly by dosing. At the outpatient postoperative visit, 52% of participants (15/29) with weight-based dosing compared with 15% (5/33) with fixed dosing achieved prophylactic peak anti-Xa level (RR 3.41, 95% CI 1.42-8.24). There were no VTEs in either group. Wound complications occurred in five individuals (7%) with weight-based enoxaparin dosing compared with one individual (1%) with fixed enoxaparin dosing (RR 4.86, 95% 0.58-40.63).

Conclusion: Weight-based dosing was more effective than fixed enoxaparin dosing in achieving prophylactic peak anti-Xa levels after cesarean delivery.

Clinical Trial Registration: ClinicalTrials.gov, NCT04305756.